Glucarpidase

• Glucarpidase is a recombinant enzyme that rapidly breaks down methotrexate.
• Its primary use is to reduce toxic methotrexate levels in patients with impaired kidney function.
• It acts by hydrolyzing methotrexate into inactive metabolites, allowing for quicker elimination.
• Common side effects include flushing, nausea, and headache, while its main benefit is preventing severe methotrexate toxicity.
• Administered intravenously, its use requires careful monitoring of methotrexate levels and patient renal function.

What is Glucarpidase and How It Works

Glucarpidase is a recombinant bacterial enzyme that functions as a carboxypeptidase. It is specifically designed to rapidly hydrolyze methotrexate, a chemotherapy drug, into inactive metabolites. This enzymatic action is critical in situations where methotrexate levels become dangerously high, posing a significant risk to patient health.

The Glucarpidase mechanism of action involves cleaving the glutamate portion of the methotrexate molecule. This process converts methotrexate into 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate, both of which are pharmacologically inactive and can be excreted by the kidneys or liver. Unlike methotrexate, which is primarily cleared by the kidneys, Glucarpidase provides an alternative pathway for methotrexate elimination, making it particularly valuable when renal function is compromised.

What is Glucarpidase Used For?

Glucarpidase is primarily used to treat toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function. High-dose methotrexate is a common chemotherapy regimen for various cancers, including osteosarcoma, leukemia, and lymphoma. However, if the kidneys cannot adequately clear methotrexate from the body, the drug can accumulate to toxic levels, leading to severe and potentially life-threatening side effects such as myelosuppression, mucositis, and liver or kidney damage.

In these critical scenarios, Glucarpidase provides a rapid and effective means to lower methotrexate concentrations, thereby mitigating the risk of severe toxicity and improving patient outcomes. It is typically administered as a single intravenous dose when conventional methods like hydration and urine alkalinization are insufficient to reduce methotrexate levels quickly enough.

Glucarpidase Side Effects, Benefits, and Drug Information

The primary benefit of Glucarpidase is its ability to rapidly and significantly reduce plasma methotrexate levels, often within minutes of administration. This rapid clearance can prevent or reverse severe methotrexate toxicity, which can otherwise lead to prolonged hospital stays, increased morbidity, and even mortality. By reducing methotrexate concentrations, Glucarpidase helps protect vital organs from damage and allows for the continuation of necessary cancer treatment once toxicity is managed.

However, like all medications, Glucarpidase can cause side effects. The Glucarpidase side effects and benefits profile includes both common and less frequent adverse reactions. Common side effects may include:

• Flushing
• Nausea and vomiting
• Headache
• Hypotension (low blood pressure)
• Paresthesia (tingling or numbness)

More serious, though rare, side effects can include allergic reactions. It is also important to note that Glucarpidase can interfere with certain methotrexate assays, leading to falsely low readings. Therefore, specific immunoassay methods that are not affected by Glucarpidase metabolites should be used for accurate methotrexate level monitoring after its administration.

Regarding Glucarpidase drug information, it is administered as an intravenous bolus injection over 5 minutes. The typical dose is 50 units per kilogram of body weight. Due to its rapid action, methotrexate levels should be monitored closely before and after administration. Leucovorin, an antidote for methotrexate, should not be administered within two hours before or after Glucarpidase, as Glucarpidase can degrade leucovorin, reducing its effectiveness. The decision to use Glucarpidase is made by oncology specialists based on the patient’s methotrexate levels, renal function, and clinical status.